Methyltransferase, trithorax (IPR016569)

Overlapping homologous superfamilies

Family relationships

Description

This entry includes a group of histone methyltransferases. The enzyme activity has been mapped to the SET domain [PMID: 12699618], originally identified in Drosophila melanogaster (Fruit fly) Su(var)3-9, E(z) and Trithorax proteins [PMID: 12039029].

The mixed lineage leukemia (MLL) gene encodes a very large nuclear protein homologous to Drosophila trithorax (Trx). MLL is required for the proper maintenance of HOX gene expression during development and hematopoiesis [PMID: 15779005]. The Trithorax group of proteins has been implicated in a variety of processes, including centromeric and telomeric silencing and cell-cycle regulation [PMID: 12447353].

The sequence conservation pattern and structural analysis of the SET domain provides clues regarding possible active site residues. There are three conserved sequence motifs in most of the SET domain, two of which had been reported earlier. The N-terminal motif (I) has characteristic glycines. The central motif (II) has a distinct pattern of polar and charged residues (Asn, His). The C-terminal motif (III) has a characteristic dyad of polar residues and the hydrophobic residue tyrosine.